Title: Actionable Knowledge to Guide Antimicrobial Stewardship Introduction: This proposal utilizes VA research resources and partnerships to identify existing information and knowledge gaps of providers in antibiotic treatment; then develops and tests an informatics intervention designed to address them. Background: Antibiotic resistance among bacteria has become a major national and global concern, including in the VA medical system. Its rise increases the risk of a mismatch between antibiotic coverage and the disease-causing pathogen, resulting in excess morbidity, cost, and death. VHA Directive 1031 mandated antibiotic stewardship programs to address these concerns; however, they must navigate between two sometimes opposing interests: patient (successful treatment) and public interests (lower resistance). Furthermore, stewardship interventions need to be adapted to local patterns of antibiotic use and resistance-a process for which the evidence base is poor. This proposal will characterize stewardship information needs, build the evidence base, and use informatics methods to support antibiotic decision- making that benefit both individual Veterans and Veteran as a whole. Career Aims: My overarching career goals are to: 1) become an independent HSRD&D investigator in the stewardship domain, 2) develop a comprehensive framework for weighing the risks and benefits of antibiotic treatment choices, and 3) architect VA systems to promote better antibiotics decisions through informatics. Research Aims: My research aims build toward my career aims: (1) Characterize the information needs and decision-making patterns of stewards when making antibiotic recommendations. (2) Identify predictors of antibiotic coverage and emergence of resistance from local antibiotic use and resistance data. (3) Develop a clinical decision-support system that nudges and prompts stewards to use local hospital data and test the influence on stewards. Methods: Aim 1 will use naturalistic decision-making methods to map the decision-making process in a way that identifies information needs and informs the design of a decision-support tool. Aim 2 will use statistical models to find predictors of antibiotic coverag and resistance. Aim 3 will develop a prototype decision-support system and test its effect on how stewards handle resistance issues in a randomized-controlled trial. In year three, I will collaborate with implementation scientists and apply for an investigator-initiated research (IIR) award to pursue my career aims and introduce stewardship tools in a multi-center study. Impact: The career plan outlined identifies the gaps between my current experience and skills and those needed to accomplish these research aims and establish a trajectory toward my career aims. It addresses the gaps through a research agenda, formal classes, and self-study in my domain of interest. The proposal also outlines a planned IIR mentioned above, as the next step on a career in the same vein. This proposal and career path will provide new insights and tools for stewardship; thereby improving effective antibiotic therapy and resistance among Veterans. Because stewardship is a special case of medication management, insights into decision-making processes and informatics solutions from this research have implications for medication management in general.